P
US8324159B2ExpiredUtilityPatentIndex 39

Erythropoietin receptor peptide formulations and uses

Assignee: DULIEGE ANNE-MARIEPriority: Jun 3, 2005Filed: Jul 23, 2008Granted: Dec 4, 2012
Est. expiryJun 3, 2025(expired)· nominal 20-yr term from priority
Inventors:DULIEGE ANNE-MARIESTEAD RICHARDLEUTHER KERSTINWOODBURN KATHRYN WYNNENASO ROBERT BARNETT
A61K 38/16C07K 17/08
39
PatentIndex Score
1
Cited by
131
References
39
Claims

Abstract

The present invention relates to peptide compounds that are agonists of the erythropoietin receptor (EPO-R). The invention also relates to therapeutic methods using such peptide compounds to treat disorders associated with insufficient or defective red blood cell production. Pharmaceutical compositions, which comprise the peptide compounds of the invention, and dosages are also provided.

Claims

exact text as granted — not AI-modified
1. A method for treating a patient having a disorder characterized by a deficiency of erythropoietin or a low or defective red blood cell population, which method comprises administering once every 3-4 weeks to the patient a therapeutically effective amount of a compound that binds to and activates an erythropoietin receptor (EPO-R),
 wherein the compound comprises: 
 (a) a first peptide monomer and a second peptide monomer, each of said first and second peptide monomers comprising the amino acid sequence
 (AcG)GLYACHMGPIT(1-nal)VCQPLR (SEQ ID NO:14); 
 
 (b) a linker moiety covalently bonding the first peptide monomer to the second peptide monomer; and 
 (c) a spacer moiety covalently joining the linker moiety and a poly(ethylene glycol) (PEG) moiety, said PEG moiety comprising a linear, unbranched PEG having a molecular weight of 10,000 to 60,000 Daltons. 
 
     
     
       2. The method of  claim 1 , wherein the compound is administered with a pharmaceutically acceptable carrier. 
     
     
       3. The method of  claim 1 , wherein the disorder is renal failure or dialysis. 
     
     
       4. The method of  claim 1 , wherein the disorder is anemia associated with a malignancy. 
     
     
       5. The method of  claim 1 , wherein the disorder is chronic kidney disease. 
     
     
       6. The method of  claim 5 , wherein the therapeutically effective amount is a dosage of 0.25 to 0.5 milligram of the compound per 1 kilogram of body weight of the patient. 
     
     
       7. The method of  claim 1 , wherein the dosage is 0.5 to 0.75 milligram of the compound per 1 kilogram of body weight of the patient. 
     
     
       8. The method of  claim 1 , wherein the therapeutically effective amount is administered once every 4 weeks. 
     
     
       9. The method of  claim 1 , wherein the therapeutically effective amount is administered by intravenous injection. 
     
     
       10. The method of  claim 1 , wherein the therapeutically effective amount is administered by subcutaneous injection. 
     
     
       11. The method of  claim 4 , wherein the therapeutically effective amount is a dosage of 0.05 to 0.5 milligram of the compound per 1 kilogram of body weight of the patient. 
     
     
       12. The method of  claim 4 , wherein the malignancy is solid tumor malignancy or lymphoma. 
     
     
       13. The method of  claim 12 , wherein the malignancy is a solid tumor malignancy selected from the group consisting of breast cancer, lung cancer and prostate cancer. 
     
     
       14. The method of  claim 4  wherein the patient is undergoing chemotherapy. 
     
     
       15. The method of  claim 14 , wherein the compound is co-administered with the chemotherapy. 
     
     
       16. The method of  claim 14 , wherein the compound is administered prior to the chemotherapy. 
     
     
       17. The method of  claim 16 , wherein the compound is administered 3-5 days before the chemotherapy. 
     
     
       18. The method of  claim 1 , wherein the amino acid sequence additionally comprises (MeG), K or (MeG)K. 
     
     
       19. The method of  claim 18 , wherein the amino acid sequence is:
 (AcG)GLYACHMGPIT(1-nal)VCQPLRK (SEQ ID NO:1). 
 
     
     
       20. The method of  claim 18 , wherein the amino acid sequence is:
 (AcG)GLYACHMGPIT(1-nal)VCQPLR(MeG) (SEQ ID ON:3). 
 
     
     
       21. The method of  claim 18 , wherein the amino acid sequence is:
 (AcG)GLYACHMGPIT(1-nal)VCQPLR(MeG)K (SEQ ID NO:2). 
 
     
     
       22. The method of  claim 1 , wherein the spacer moiety is an iminodiacetic moiety. 
     
     
       23. The method of  claim 1 , wherein the spacer moiety has the formula: 
       
         
           
           
               
               
           
         
       
       wherein R 4  is selected from the group consisting of NHCO, CO, COO and NHCOO. 
     
     
       24. The method of  claim 1 , wherein the linker moiety is lysine. 
     
     
       25. The method of  claim 1 , wherein the PEG moiety has a molecular weight of 10,000 to 50,000 Daltons. 
     
     
       26. The method of  claim 25 , wherein the PEG moiety has a molecular weight of 20,000 to 40,000 Daltons. 
     
     
       27. A method for treating a patient having a disorder characterized by a deficiency of erythropoietin or a low or defective red blood cell population, which method comprises administering once every 3-4 weeks to the patient a therapeutically effective amount of a compound according to Formula I: 
       
         
           
           
               
               
           
         
       
       wherein PEG 20k-50k  is a polyethylene glycol moiety having a molecular weight of about 20,000 to about 50,000 Daltons. 
     
     
       28. A method for treating a patient having a disorder characterized by a deficiency of erythropoietin or a low or defective red blood cell population, which method comprises administering once every 3-4 weeks to the patient a therapeutically effective amount of a compound according to Formula IA: 
       
         
           
           
               
               
           
         
       
       whereinPEG 20k  is a polyethylene glycol moiety having a molecular weight of about 20,000 Daltons. 
     
     
       29. The method of  claim 27  or  28 , wherein the disorder is anemia associated with a malignancy. 
     
     
       30. The method of  claim 29 , wherein the malignancy is a solid tumor malignancy selected from the group consisting of breast cancer, lung cancer and prostate cancer. 
     
     
       31. The method of  claim 29 , wherein the patient is undergoing chemotherapy. 
     
     
       32. The method of  claim 31 , wherein the compound is co-administered with the chemotherapy. 
     
     
       33. The method of  claim 31 , wherein the compound is administered prior to the chemotherapy. 
     
     
       34. The method of  claim 33 , wherein the compound is administered 3-5 days before the chemotherapy. 
     
     
       35. The method of  claim 29 , wherein the therapeutically effective amount is a dosage of 0.075 to 0.5 milligram of the compound per 1 kilogram of body weight of the patient. 
     
     
       36. The method of  claim 35 , wherein the dosage is 0.2 to 0.4 milligram of the compound per 1 kilogram of body weight of the patient. 
     
     
       37. The method of  claim 27  or  28 , wherein the disorder is renal failure or dialysis. 
     
     
       38. The method of  claim 37 , wherein the therapeutically effective amount is a dosage of 0.025 to 0.2 milligram of the compound per 1 kilogram of body weight of the patient. 
     
     
       39. The method of  claim 38 , wherein the dosage is 0.05 to 0.1 milligram of the compound per 1 kilogram of body weight of the patient.

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